Abstract
BACKGROUND: Approximately one-third of patients with advanced colorectal cancer (CRC) and treated with bevacizumab are prescribed proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs). However, there is limited data on the effects of PPIs and H2RAs in these patients. To investigate the oncological outcomes of PPI and H2RA use in CRC patients treated with bevacizumab, we performed a retrospective cohort study using the Taiwan National Health Insurance Research Database and Taiwan Cancer Registry Database from 2005 to 2020. METHODS: In CRC patients treated with bevacizumab, the PPI users and H2RA users were matched with patients without acid-reducing agents (ARAs) by 1:4 propensity score matching. PPI users and H2RA users were matched with propensity scoring in a 1:1 ratio. We divided patients into 4 cumulative PPI dosage levels to assess the dose-response relationship. The primary endpoints were 5-year overall survival and cancer-specific survival. RESULTS: Compared with ARA non-users, both H2RA users and PPI users were associated with reduced overall survival. PPI users were associated with more significant negative effects on overall survival. Compared with H2RA users, PPI users were associated with lower 5-year overall survival (aHR: 1.19, 95% CI: 1.09-1.31) and cancer-specific survival (aHR: 1.20, 95% CI: 1.09-1.31). A similar dose-response relationship was observed for PPI users in terms of 5-year overall survival and cancer-specific overall survival. CONCLUSIONS: Compared to H2AR use, PPI use was associated with dose-dependent poorer oncological outcomes in metastatic CRC patients treated with bevacizumab.